This invention relates to bioreactor systems and to the fluid processing and sensing components used in such systems.
Bioreactor systems are increasingly being used for the synthesis of biological products. An exemplary bioreactor system employs a hollow fiber bioreactor cartridge having a multitude of semipermeable fibers that serve as a support and a nutrient conduit for cell culture. Cells are typically grown on the outside of the semipermeable fibers and are maintained by perfusion of nutrient medium which is circulated within the fibers. Waste products excreted by the cultured cells perfuse into the fibers and are carried away in the nutrient medium. Desirable cellular by-products, such as monoclonal antibodies, are typically too large to perfuse into the fibers and are thus trapped in the extracapillary region of the bioreactor cartridge.
The process control tasks associated with operation of a bioreactor system are very demanding. In many applications, the desired cell by-products are produced at an extremely slow rate. Sometimes the system must operate continuously for weeks or months at a time in order to accumulate a fraction of a gram of usable product. Any malfunction in the system can have long lasting repercussions on a project. Accordingly, it is crucial that all process control components be able to work continuously and reliably for extended periods of time with a minimum of human supervision and intervention.
The reliability of prior art bioreactors suffers by reason of the complex subsystems typically incorporated therein. An exemplary system may include a large incubator and three or more pumps. One pump is used to circulate nutrient fluid from a reservoir through the bioreactor. A second pump is used to add fresh nutrient fluid to the reservoir. A third pump is used to remove spent nutrient fluid from the reservoir. A fourth pump is used to circulate a warm water bath which surrounds the nutrient fluid reservoir. Such complicated systems are inherently susceptible to reliability problems when operated over extended periods of time.
Related to the reliability concern is that of maintaining absolute sterility. The introduction of virtually any foreign body into the system will fatally disrupt its operation. Accordingly, it is desirable that bioreactor design be oriented so as to minimize opportunities for the system to become contaminated.
Accordingly, a need remains for improved bioreactor systems.